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According to a large-scale genomic analysis of the most common and aggressive type of ovarian cancer, researchers from Memorial Sloan Kettering Cancer Center and other centers within The Cancer Genome Atlas (TCGA) project identified genetic mutations and pathways that distinctly set the disease apart not only from other types of ovarian cancer, but from other solid tumors as well. Reported in the journal Nature this week, the findings may be useful in helping doctors to choose experimental treatments that are most likely to effectively target molecular alterations in patients with this type of ovarian cancer, called high-grade serous ovarian adenocarcinoma.

Part of The Cancer Genome Atlas project (funded by the National Cancer Institute and the National Human Genome Research Institute), this collaborative study is one of the most comprehensive national efforts to collect, process, and analyze the largest set of solid tumor samples to date using state-of-the-art genomic and molecular techniques. Memorial Sloan Kettering provided the greatest number of ovarian tumor samples for the research, contributing more than 20 percent of all tissue samples analyzed in the study. It also served as one of the centers that generated and analyzed the genomic data in the study.

The investigators analyzed genetic abnormalities in nearly 500 high-grade serous ovarian tumors. They found mutations in a gene called TP53 in 96 percent of the samples. Mutations in nine other genes including NF1, BRCA1, BRCA2, RB1, and CDK12, although less prevalent, were also shown to play an important role in this disease. Researchers at Memorial Sloan Kettering are building on the findings by studying whether some of these genetic alterations affect the way cells behave and respond to certain targeted agents.

In particular, the Memorial Sloan Kettering team showed that alterations in BRCA1, BRCA2, and related genes, which predict responsiveness to a new class of agents called PARP inhibitors, are present in a larger proportion of ovarian cancer patients than previously thought. They are now translating these findings into clinically useful tests that may be applied to ongoing and planned clinical trials.

The Memorial Sloan Kettering TCGA Cancer Genome Characterization Center (one of the centers in the study that generated the genomic data) was led by molecular pathologist Marc Ladanyi, MD, and the Memorial Sloan Kettering TCGA Genome Data Analysis Center (one of the centers that analyzed the genomic data) was directed by computational biologist Chris Sander, PhD. Gynecologic oncologist and surgeon Douglas A. Levine, MD, served as principal investigator of Memorial Sloan Kettering’s TCGA Tissue Source Site and was Co-Chair of the TCGA Ovarian Disease Working Group. Dr. Levine is available to discuss the findings.

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